LGC today Home of the UK's designated National Measurement Institute and the UK Government Chemist
Measurement research
Regulatory services
Reference measurement services
Standards development
Training and consultancy
Scientific programme management
Reference Materials at LGC
• Worldwide distributor of reference materials from
numerous producers
• In-house RM production facilities:
– The NMI facility at Teddington, UK
– Two laboratories in the US:
• New Hampshire – oil based and aqueous standards
• Denver – metal CRMs
– Gemany – pharmaceutical standards
– India – pharmaceutical standards
LGC locations Edinburgh N. IRELAND St Petersburg UK Wakefield Tamworth Bromsgrove Hoddesdon Twickenham Teddington Luckenwalde POLAND Lomianki NETHERLANDS Wesel Shanghai GERMANY REPUBLIC Molsheim Szentendre Cluj-Napoca Manchester Istanbul USA Lexington Barcelona UAE SOUTH AMERICA Ahmadabad Sao Paulo Hyderabad Bangalore SOUTH AFRICA LGC's national roles National Measurement Government Chemist Institute (NMI)
Referee Analyst (4 Acts of
Delivers world-class
measurement science: a leading
Adviser to government and
NMI for chemistry & bioanalysis
industry on regulations &
Provides traceable and accurate
scientific input
standards of measurement for
"Using sound analytical
use in industry, academia and
science in support of policy and regulation"
Active involvement in CCQM,
RMO, ISOREMCO, etc
Range of capabilities listed on CMC1 and JCTLM2 databases
1 http://kcdb.bipm.org/AppendixC 2 http://www.bipm.org/jctlm
Scientific Capabilities: Inorganic
• High accuracy quantitative analysis by ICP-MS
• Speciation analysis (quantitative & identification) by LC-
ICP-MS, GC-ICP-MS and ion trap LC-MS
• Nano-particle analysis using field flow fractionation FFF-
• Solid sampling and imaging using laser ablation ICPMS
• Isotope ratio determination by multi-collector ICP-MS
Scientific Capabilities: Organic
• High accuracy quantitative analysis by LC-MS/MS
• High mass accuracy identification using ion traps and
time of flight instruments
• Specialist separation techniques including nano LC,
multidimensional GC, ion mobility
• Imaging capability using MALDI-TOF-TOF and DESI
• Quantitative and structural analysis of proteins and
• High accuracy purity assessment using a range of
classical techniques and qNMR
Scientific Capabilities: Biological
• Next generation sequencing:
– High accuracy sequencing and differentiation of microbial
• Foods analysis
– High accuracy quantification of GMOs - NRL status
– Detection of food fraud and food adulteration
• MiRNA analysis:
– High accuracy mi RNA quant
– Development of prototype reference materials
• Cell analysis:
– High accuracy cellular imaging and metrology
– Nanotoxicology and toxicology
Isotope Dilution Mass Spectrometry
• The sample is spiked with a solution of an isotopic
analogue of the analyte of interest (= sample blend)
• A calibration standard is spiked with the same solution
as the sample (= calibration blend)
• Sample blends and calibration blends are prepared such
– the isotope ratios in the blends are the same
– the intensities of the peaks in the blends are the sa
Exact Matching Double IDMS Advantages of IDMS
• the spike material is the ideal internal standard as it
behaves in exactly the same way as the analyte
• once equilibrated, any losses due to the sample
preparation do not affect the result
• the effects of mass bias and linearity are eliminated
since they affect both calibration and sample blends
• accurate quantification of the isotopic analogue is not
• potential for high accuracy and low & well-defined
Limitations of IDMS
• an iterative process as the analyte concentration must
be determined before exact matching can occur
• equilibration between the analyte and the isotopic
analogue must occur before extraction. For organic extractions, extensive equilibrium studies must be performed
• traceability is through the calibration standard (hence the
emphasis on purity determination)
• there must be no significant conversion of compounds
during extraction
→Time-consuming and expensive.
CRM Production within the NMI
Accredited to ISO-Guide 34
Pure RM production for >20 years
• Matrix materials
• Single substance organic
– Melting point
– Enthalpy of fusion
– Elemental content
European Reference Materials (ERM) A joint collaboration of three major European reference materials producers (IRMM, BAM & LGC) Peer-review of CRMs by the European Reference Materials technical committee ensures highest quality and reliability Full transparency of the certification principles and the evaluation report provides valuable insight to help analysts get the maximum benefit from the use of the material.
Clearly defined and stated traceability of the certified values ensures applicability of the materials to the respective analytical problem. Internationally recognised values underpinned through the participation of the producing institutes in the key comparisons organised by the BIPM Characterisation Approaches
• Single Primary (Definitive) Method
– Utilises NMI capabilities eg isotope dilution mass spec
• Consensus certification
– Multiple laboratory study
– Typically benefits from robust estimates
• Two or More Independent Methods
– Requires detailed uncertainty information for methods
– Particular problems with ‘between-method' effects
Approaches to Stability Assurance
Prior information
– Use Published and/or Readily
Available Information
– Use of Data from Related
• materials, packaging and
New Stability studies
– Accelerated testing – Long-term testing
• Isochronous testing
Determine a value for ults
= the equivalence of the mathematical relationships
between the results of different measurement procedures for a RM and for representative samples from healthy and diseased individuals
• Particularly relevant for clinical CRMs where method
used for certification (eg IDMS) may be very different from routine methods (eg assay)
• Important component of CRM certification
All materials distributed through LGC Standards
All stored in controlled conditions mostly in the UK
Additional world-wide warehousing is imminent
Customer Support
Expertise / knowledge available for lifetime of material
All enquiries are collated and stored
Trace metals in biological CRMs
The analysis of trace metals in biological matrices such as serum or urine is performed routinely
These can be performed as part of clinical studies; as indicators or disease or organ function or as indictors of artificial joint corrosion
ERM-DA120a1 has been certified for content of Cu, Se & Zn and will soon be additionally certified for Ca, Fe, K, Mg and selenomethionine
We are also planning to certify a blood CRM for Co & Cr content in response to a recent MHRA directive2 that recommends blood level monitoring for metal-on-metal hip-replacement patients and
additional remedial action if Co & Cr levels are observed at > 7
Therapeutic drug monitoring of immunosuppressants
Immunosuppressants such as tacrolimus, sirolimus and ciclosporin ar
e primarily used to prevent rejection of organ transplants
Potent compounds with very severe side-effects
Patients monitored monthly to check levels in blood in therapeutic
range: e.g. tacrolimus therapeutic range is typically 3 – 15 ng/mL
A variety of techniques are used in clinical laboratories including immunoassay and mass spectrometry
There are no reliable standards and clinicians cannot compare data obtained from different laboratories
LGC have released a CRM of tacrolimus in whole blood using an isotope dilution method and provided reference measurements to 2 assay kit producers.Other clinically relevant CRMs
A range of high purity organic compounds to be used for calibration purposes, eg digoxin, theophylline, etc
A range of ethanol solutions used for blood alcohol and breath analyser calibration
ERM-DA200 & 201 Digoxin in serum
ERM-DA250 to 253 Creatinine & Electrolytes in serum
• ERM-DA345 & 346 Testosterone in serum
LGC is active in provision of high accuracy measurement services and certified reference materials
We are keen to receive feedback from RM users about what materials are required
Thank you for your attention